NCT01109537

Brief Summary

The purpose of the study is to understand the brain chemistry of people with Restless Legs Syndrome (RLS). The primary hypothesis is that patients with RLS will have reduced GABA levels in their Thalamus and elevated Glutamate levels in their Anterior Cingulate Cortex. The study will use MRS imaging to examine the regional levels of these neurochemicals, GABA and Glutamate, in the brain.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
75

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Apr 2010

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2010

Completed
21 days until next milestone

First Submitted

Initial submission to the registry

April 22, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 23, 2010

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
Last Updated

January 7, 2015

Status Verified

January 1, 2015

Enrollment Period

4.1 years

First QC Date

April 22, 2010

Last Update Submit

January 6, 2015

Conditions

Restless Legs Syndrome

Keywords

Restless Legs Syndrome (RLS)GABAGlutamateMagnetic Resonance Spectroscopy

Outcome Measures

Primary Outcomes (1)

  • Regional GABA and glutamate levels derived from 4T MRS.

    2 years

Study Arms (2)

RLS Diagnosis

Healthy Controls

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Male and female subjects who have RLS or are normal controls will be recruited from the greater Boston metropolitan area. We anticipate enrolling 70 subjects with RLS and 70 normal controls, under a plan to complete 15 subjects in each group.

You may qualify if:

  • Subjects at least 18 years of age
  • Subjects with a diagnosis of RLS using the International RLS Study Group (IRLSSG) criteria
  • Subjects with a history of RLS symptoms at least 15 nights in the prior month, or, if on treatment, this frequency of symptoms before treatment was started

You may not qualify if:

  • Subjects who are unable to discontinue prohibited medications prior to sleep study and 1H-MRS. These include any CNS-active medications. For RLS subjects, RLS-related medications (e.g. dopaminergic agents and alpha 2-delta agents) must be discontinued a minimum of 48 hours prior to PSG. In the RLS group, benzodiazepines must be discontinued a minimum of one week prior to PSG. For normal controls with regular treatment (\>1 time/wk) with CNS active agents within 1 month of screening visit will also be excluded.
  • Subjects with an active or unstable major psychiatric disorder requiring further treatment (e.g., major depressive disorder). Subjects with clinically significant depression, or with clinically significant anxiety, or who, in the investigator's judgment might require intervention with either pharmacological or non-pharmacological therapy over the course of the study.
  • Subjects with clinical evidence of any untreated moderate to severe sleep disorder other than RLS (forRLS group) (e.g. obstructive sleep apnea, insomnia, narcolepsy, delayed sleep phase syndrome, etc.) within the preceding year
  • Subjects with an apnea-hypopnea index (AHI) \> 15 at the polysomnography visit
  • Subjects who consume beverages containing more than 400mg of caffeine per day
  • Subjects who consume more than 14 alcoholic units in any week, or more than 5 alcoholic units in any single day, over the month preceding the screening visit.
  • Females who are pregnant or lactating
  • Subjects with a history of neurologic illness (e.g. brain neoplasm, multiple sclerosis), significant or unstable medical illness (e.g. congestive heart failure, diabetes mellitus), or history of significant head trauma or loss of consciousness \> 30 minutes
  • Subjects who have positive urine drug screening (phencyclidine, cocaine, amphetamines, tetrahydrocannabinol, and opiates) at the screening visit or at the MRS visit.
  • Contraindications to MRS scans, including:
  • Cardiac pacemakers
  • Aneurysm clips and other vascular stents, filters, clips or other devices
  • Prosthetic heart values
  • Other prostheses
  • Neuro-stimulator devices
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sleep HealthCenters

Brighton, Massachusetts, 02135, United States

Location

Related Publications (8)

  • Bucher SF, Seelos KC, Oertel WH, Reiser M, Trenkwalder C. Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol. 1997 May;41(5):639-45. doi: 10.1002/ana.410410513.

    PMID: 9153526BACKGROUND

  • Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science. 2000 Jun 9;288(5472):1769-72. doi: 10.1126/science.288.5472.1769.

    PMID: 10846154BACKGROUND

  • Cervenka S, Palhagen SE, Comley RA, Panagiotidis G, Cselenyi Z, Matthews JC, Lai RY, Halldin C, Farde L. Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. Brain. 2006 Aug;129(Pt 8):2017-28. doi: 10.1093/brain/awl163. Epub 2006 Jul 1.

    PMID: 16816393BACKGROUND

  • von Spiczak S, Whone AL, Hammers A, Asselin MC, Turkheimer F, Tings T, Happe S, Paulus W, Trenkwalder C, Brooks DJ. The role of opioids in restless legs syndrome: an [11C]diprenorphine PET study. Brain. 2005 Apr;128(Pt 4):906-17. doi: 10.1093/brain/awh441. Epub 2005 Feb 23.

    PMID: 15728657BACKGROUND

  • Spiegelhalder K, Feige B, Paul D, Riemann D, van Elst LT, Seifritz E, Hennig J, Hornyak M. Cerebral correlates of muscle tone fluctuations in restless legs syndrome: a pilot study with combined functional magnetic resonance imaging and anterior tibial muscle electromyography. Sleep Med. 2008 Jan;9(2):177-83. doi: 10.1016/j.sleep.2007.03.021. Epub 2007 Jul 16.

    PMID: 17638594BACKGROUND

  • Etgen T, Draganski B, Ilg C, Schroder M, Geisler P, Hajak G, Eisensehr I, Sander D, May A. Bilateral thalamic gray matter changes in patients with restless legs syndrome. Neuroimage. 2005 Feb 15;24(4):1242-7. doi: 10.1016/j.neuroimage.2004.10.021. Epub 2004 Dec 8.

    PMID: 15670702BACKGROUND

  • Winkelman JW, Redline S, Baldwin CM, Resnick HE, Newman AB, Gottlieb DJ. Polysomnographic and health-related quality of life correlates of restless legs syndrome in the Sleep Heart Health Study. Sleep. 2009 Jun;32(6):772-8. doi: 10.1093/sleep/32.6.772.

    PMID: 19544754BACKGROUND

  • Kushida CA, Allen RP, Atkinson MJ. Modeling the causal relationships between symptoms associated with restless legs syndrome and the patient-reported impact of RLS. Sleep Med. 2004 Sep;5(5):485-8. doi: 10.1016/j.sleep.2004.04.004.

    PMID: 15341894BACKGROUND

MeSH Terms

Conditions

Restless Legs Syndrome

Condition Hierarchy (Ancestors)

Nervous System DiseasesSleep Disorders, IntrinsicDyssomniasSleep Wake DisordersParasomniasMental Disorders

Study Officials

  • John W Winkelman, MD, PhD

    Sleep Health Centers, Brigham and Women's Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Psychiatry, Harvard Medical School

Study Record Dates

First Submitted

April 22, 2010

First Posted

April 23, 2010

Study Start

April 1, 2010

Primary Completion

May 1, 2014

Study Completion

May 1, 2014

Last Updated

January 7, 2015

Record last verified: 2015-01

Locations

US(1)